Probiotic Spore Inspired Oral Drug Delivery System With Multiple‐Barriers‐Crossing Ability Modulates Gut‐Brain Axis for Parkinson's Disease Therapy
5 affiliations
- 1School of Pharmaceutical Sciences State Key Laboratory of Antiviral Drugs Pingyuan Laboratory Zhengzhou University Zhengzhou China
- 2Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases Zhengzhou China
- 3Hubei Provincial Clinical Research Center for Central Nervous System Repair and Functional Reconstruction Taihe Hospital Hubei University of Medicine Shiyan Hubei China
- 4Department of Pharmacy Henan General Hospital Zhengzhou China
- 5School of Electrical Mechanical and Biomedical Engineering Faculty of Engineering and Information Technology University of Technology Sydney Sydney New South Wales Australia
Abstract
For Parkinson's disease (PD), the development of oral brain‐targeted drug delivery is challenging due to various physiological barriers. Besides the brain, the effect of the gut on the microbiome‐gut‐brain axis should not be ignored. Therefore, developing a gut‐brain dual‐targeted delivery system with multiple‐barriers‐crossing ability is meaningful. During the germination of probiotic spores, we find that spore coat proteins (SP) shed from their surface possess excellent characteristics (re‐assembling into nanoparticles, multiple‐barriers penetration ability, antioxidant property, etc.), offering potential for brain‐targeted drug delivery. Inspired by this, we propose a probiotic spore based oral drug delivery system to dual‐regulate the gut‐brain. After oral administration, the spore system crosses the harsh gastrointestinal chemical barrier. Spores germinate in the intestine into probiotics to modulate the gut‐brain axis. Meanwhile, the SP‐derived reassembled nanosystems cross multiple barriers (intestinal mucus barrier, enterocyte barrier, blood‐brain barrier) to reach brain and further reduce oxidative stress. Notably, neurodegeneration and behavioral deficits are alleviated in PD mice. Such gut‐brain dual‐regulation strategy emphasizes a comprehensive and promising technique for central nervous system disease treatment, which may be an alternative to traditional single‐targeted methods. Furthermore, the probiotic spore‐based oral biotherapeutics with multiple‐barriers‐crossing efficiency provide new insight into other brain diseases.
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BibTeX
@article{feng2026probiotic,
title = {{Probiotic Spore Inspired Oral Drug Delivery System With Multiple‐Barriers‐Crossing Ability Modulates Gut‐Brain Axis for Parkinson's Disease Therapy}},
author = {Qianhua Feng and Yuying Mei and Jia Zhang and Liying Sun and Bingqian Si and Huimin Zhou and Huifang Xiao and Runhan Liu and Jieyun Zhang and Lei Wang},
journal = {Exploration},
year = {2026},
month = sep,
doi = {10.1002/exp2.70221},
url = {https://doi.org/10.1002/exp2.70221},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Probiotic Spore Inspired Oral Drug Delivery System With Multiple‐Barriers‐Crossing Ability Modulates Gut‐Brain Axis for Parkinson's Disease Therapy
AU - Qianhua Feng
AU - Yuying Mei
AU - Jia Zhang
AU - Liying Sun
AU - Bingqian Si
AU - Huimin Zhou
AU - Huifang Xiao
AU - Runhan Liu
AU - Jieyun Zhang
AU - Lei Wang
PY - 2026
DA - 2026/09/09
JO - Exploration
DO - 10.1002/exp2.70221
UR - https://doi.org/10.1002/exp2.70221
AB - For Parkinson's disease (PD), the development of oral brain‐targeted drug delivery is challenging due to various physiological barriers. Besides the brain, the effect of the gut on the microbiome‐gut‐brain axis should not be ignored. Therefore, developing a gut‐brain dual‐targeted delivery system with multiple‐barriers‐crossing ability is meaningful. During the germination of probiotic spores, we find that spore coat proteins (SP) shed from their surface possess excellent characteristics (re‐assembling into nanoparticles, multiple‐barriers penetration ability, antioxidant property, etc.), offering potential for brain‐targeted drug delivery. Inspired by this, we propose a probiotic spore based oral drug delivery system to dual‐regulate the gut‐brain. After oral administration, the spore system crosses the harsh gastrointestinal chemical barrier. Spores germinate in the intestine into probiotics to modulate the gut‐brain axis. Meanwhile, the SP‐derived reassembled nanosystems cross multiple barriers (intestinal mucus barrier, enterocyte barrier, blood‐brain barrier) to reach brain and further reduce oxidative stress. Notably, neurodegeneration and behavioral deficits are alleviated in PD mice. Such gut‐brain dual‐regulation strategy emphasizes a comprehensive and promising technique for central nervous system disease treatment, which may be an alternative to traditional single‐targeted methods. Furthermore, the probiotic spore‐based oral biotherapeutics with multiple‐barriers‐crossing efficiency provide new insight into other brain diseases.
SN - 2766-8509
SN - 2766-2098
ER -